EP1933849B1 - Utilisation d'ivermectine pour le traitement des pathologies ophtalmiques - Google Patents

Utilisation d'ivermectine pour le traitement des pathologies ophtalmiques Download PDF

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Publication number
EP1933849B1
EP1933849B1 EP06842320.1A EP06842320A EP1933849B1 EP 1933849 B1 EP1933849 B1 EP 1933849B1 EP 06842320 A EP06842320 A EP 06842320A EP 1933849 B1 EP1933849 B1 EP 1933849B1
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EP
European Patent Office
Prior art keywords
treatment
ivermectin
eye
composition
pharmaceutical composition
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP06842320.1A
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German (de)
English (en)
Other versions
EP1933849A2 (fr
Inventor
Alexandre Kaoukhov
Christophe Villard
Philippe Bouissou
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Galderma SA
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Galderma SA
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Priority claimed from FR0510025A external-priority patent/FR2891460B1/fr
Application filed by Galderma SA filed Critical Galderma SA
Priority to EP12152476.3A priority Critical patent/EP2455085B1/fr
Publication of EP1933849A2 publication Critical patent/EP1933849A2/fr
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Publication of EP1933849B1 publication Critical patent/EP1933849B1/fr
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/14—Decongestants or antiallergics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/14—Ectoparasiticides, e.g. scabicides

Definitions

  • the present invention relates to the use of ivermectin in the preparation of a pharmaceutical composition intended for the treatment of ocular rosacea.
  • Ocular rosacea is frequently diagnosed when it coexists with cutaneous signs or symptoms of rosacea ( Browning D.J. and Proia A. D., Ocular Rosacea, Surv. Ophthalmol., 1986, 31, 145-58 ). Ocular rosacea is independent of the severity of rosacea of the skin ( Donshik P. C, Hoss D.M. and Ehlers W.H., Inflammatory and papulosquamous disorders of the skin and eye, Dermatologic Clinics, 1992, 3, 533-47 ).
  • ocular signs and symptoms can occur before the cutaneous manifestations.
  • the relevant symptoms for the diagnosis of ocular rosacea are as follows: feeling of burning or of smarting, feeling of a foreign body, feeling of dryness of the eye, increased sensitivity to light, blurred vision.
  • the least serious clinical signs in patients affected by ocular rosacea are telangiectasia of the eyelid margin, meibomitis, chalazia, conjunctival hyperaemia and papillary conjunctivitis ( Donshik P. C, Hoss D.M.
  • the causes of the ocular pathologies mentioned above include in particular the presence of various organisms, such as Demodex folliculorum, the commonest human ectoparasite. However, not all ocular pathologies are related to the presence of this ectoparasite.
  • ocular rosacea which is included among ophthalmic pathologies, is not treated, serious complications may occur in the cornea and this can detrimentally affect the vision.
  • the therapeutic measures commonly used are the application of hot compresses and of topical antibiotics, such as a metronidazole gel, for example. A marked improvement is obtained but is often followed by a relapse in the form of conjunctivitis.
  • Oral antibiotics such as tetracycline hydrochloride or doxycycline
  • the level of relapse is of the order of 66% after treatment for 6 months ( Switzerland K.A., Palay D.A. and Rock B., Dermatologic diagnosis and treatment of itchy red eyelids, Surv. Ophthalmol., 1996, 40, 293-306 ).
  • a maintenance treatment is often necessary, sometimes for several years, indeed even for life.
  • Cyclines have an anti-inflammatory action but do not have a curative action. The longer the treatment, the more there exists a risk of appearance of resistance ( Quaterman M.J., Johnson D. W., Abele D. C, Lesher J.L., Hull D. S. and Davis L.
  • An antibiotic of the class of the macrolides (erythromycin) can also be used but the response to the treatment is not systematic.
  • Ivermectin is a mixture of two compounds belonging to the class of the avermectins, 5-O-demethyl-22,23-dihydroavermectin A 1a and 5-O-demethyl- 22, 23-dihydroavermectin A 1b . They are also known under the names of 22,23-dihydroavermectin B 1a and 22,23-dihydroavermectin B 1b . Ivermectin comprises at least 80% of 22,23-dihydroavermectin B 1a and less than 20% of 22,23-dihydroavermectin B 1b .
  • This active agent forms part of the class of the avermectins, a group of macrocyclic lactones produced by the bacterium Streptomyces avermitilis ( Reynolds J. E. F. (Ed), (1993) Martindale, The Extra Pharmacopoeia, 29th Edition, Pharmaceutical Press, Lond on).
  • ivermectin was presented as a broad-spectrum antiparasitic medicament for veterinary use ( Campbell W. C. et al. (1983), Ivermectin: a potent new antiparasitic agent, Science, 221, 823-828 ). It is effective against the majority of common intestinal worms (except for the Teniae), the majority of the acarids and a few lice. It exhibits in particular a high affinity for the glutamate-dependent chloride channels present in the nerve and muscle cells of invertebrates. Its attachment to these channels promotes an increase in the membrane permeability to chloride ions, resulting in hyperpolarization of the nerve or muscle cell.
  • Ivermectin also interacts with other ligand- dependent chloride channels, such as those involving the GABA ( ⁇ -aminobutyric acid) neuromediator.
  • GABA ⁇ -aminobutyric acid
  • Ivermectin is more particularly an anthelmintic. It is already described in man in the treatment of onchocerciasis due to Onchocerca volvulus, of gastrointestinal strongyloidiasis (product Stromectol ® and of human scabies ( Meinking T. L. et al., N. Engl. J. Med., 1995, Jul., 6, 331(1), 26-30 , The treatment of scabies with ivermectin) and in the treatment of microfilaraemia diagnosed or suspected in subjects affected by lymphatic filariasis due to Wuchereria bancrofti.
  • Patent US 6 133 310 discloses the use of invermectin topically in the treatment of rosacea of the skin, in the form of a prototype of a lotion composed of a mixture of invermectin and of water, and also mentions the possibility of a prototype of a cream composed, for its part, of the mixture of invermectin and of an excipient, such as propylene glycol or sodium lauryl sulphate, but does not describe any- pharmaceutical composition as such.
  • These mixtures are similar to experimental preparations to be applied to the skin, used in the context of first results of a proof of concept.
  • the facts disclosed in this patent do not teach a person skilled in the art anything regarding the feasibility and the effectiveness of pharmaceutical compositions acceptable industrially in the treatment of ocular rosacea.
  • ivermectin is suitable for the treatment of ocular rosacea.
  • treatment is understood to mean, according to the invention, treatment in man.
  • a subject-matter of the present invention is thus the use of ivermectin in the preparation of a unique, non-irritating, pharmaceutical composition intended for the treatment of ocular rosacea.
  • composition is understood to mean, according to the invention, a stable composition comprising a therapeutically active agent which has a good cosmetic quality and a satisfactory time limit (18 months minimum).
  • the term "unique pharmaceutical composition” is understood to mean that the composition comprising ivermectin is used alone to treat ocular rosacea ; combinations with other pharmaceutical compositions are thus excluded.
  • ivermectin is the only active principle used in the composition for treating ocular rosacea; no active principle other than ivermectin, whether in particular administered topically or orally, is used according to the invention.
  • the pharmaceutical composition according to the invention comprising ivermectin, is intended in particular for the treatment of ophthalmic symptoms, symptoms chosen from a feeling of burning or of smarting of the eye, a feeling of a foreign body in the eye, a feeling of dryness of the eye, an increased sensitivity to light, blurred vision, telangiectasia of the eyelid margin, meibomitis, chalazia, conjunctival hyperaemia and papillary conjunctivitis.
  • the pharmaceutical composition according to the invention comprising ivermectin is intended in particular for the treatment of conjunctivitis or blepharitis.
  • the pharmaceutical composition according to the invention is intended for the treatment of the eyes topically .
  • the topical application represents the commonest method of administration of ophthalmic medicaments.
  • the topical route makes possible the application in the eye of eyewashes .
  • This composition for topical application can be provided in anhydrous form, in aqueous form or in the form of an emulsion.
  • the pharmaceutical composition for topical use must be nonirritating and compatible with the tissues of the eye.
  • the solutions are sterile preparations free from all particles.
  • composition according to the invention preferably comprises from ivermectin, by weight with respect to the total weight of the composition.
  • the composition according to the invention is provided in the form of an eyewash.
  • eyewash is understood to mean a liquid formulation specifically appropriate for administration to the conjunctiva of the eye and to the cornea.
  • the eyewash is characterized by a volume of the instilled drops of approximately 25-50 microlitres.
  • compositions according to the invention have to meet specific conditions in order to be able to be applied in the eye.
  • Such conditions include in particular sterility, absence of irritation and compatibility with the tissues of the eye.
  • the latter criterion is more difficult to obtain than for a composition applied to the skin; in particular, compounds such as ethanol or glycols, formulated in compositions to be applied to the skin, cannot be present in compositions for ocular use.
  • the topical compositions according to the invention make it possible to directly and specifically treat the symptoms of the pathology in the eye and eyelids by a local action; in particular, since only the eye is targeted, a better effectiveness can be expected.
  • the topical compositions according to the invention preferably being the only ones administered to treat ocular rosacea, interactions between active principles can be reduced, indeed even avoided.
  • composition according to the invention can additionally comprise inert additives or combinations of these additives, such as
  • compositions comprising ivermectin will now be given, by way of illustration and without any limiting nature.

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  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Ophthalmology & Optometry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Claims (3)

  1. Utilisation d'ivermectine en tant que principe actif unique dans la préparation d'une composition pharmaceutique unique non irritante pour le traitement de la rosacée oculaire, caractérisée en ce que la composition est administrée localement et se présente sous la forme d'un lavage oculaire ; la composition comprenant de 0,01 à 5 % en poids d'ivermectine par rapport au poids total de la composition.
  2. Utilisation selon la revendication 1, caractérisée en ce que la composition pharmaceutique est destinée au traitement de symptômes parmi une sensation de brûlure ou de picotement dans l'oeil, une sensation d'un corps étranger dans l'oeil, une sensation de sécheresse de l'oeil, une sensibilité accrue à la lumière, une vision floue, une télangiectasie du bord des paupières, la meibomite, la blépharite, les chalazions, l'hyperémie conjonctive et la conjonctivite papillaire.
  3. Utilisation selon la revendication 1 ou 2, caractérisée en ce que la composition pharmaceutique est pour le traitement de la blépharite ou de la conjonctivite.
EP06842320.1A 2005-09-30 2006-09-29 Utilisation d'ivermectine pour le traitement des pathologies ophtalmiques Active EP1933849B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP12152476.3A EP2455085B1 (fr) 2005-09-30 2006-09-29 Utilisation topique par application dans l'oeil de l'ivermectine, pour le traitement des pathologies ophtalmiques

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
FR0510025A FR2891460B1 (fr) 2005-09-30 2005-09-30 Utilisation d'au moins un compose de la famille des avermectines pour le traitement des pathologies ophtalmiques dues au demodex folliculorum.
US72532005P 2005-10-12 2005-10-12
US81831606P 2006-07-05 2006-07-05
PCT/IB2006/003864 WO2007054822A2 (fr) 2005-09-30 2006-09-29 Utilisation d'au moins un compose de la famille des avermectines ou des milbemycines pour le traitement de pathologies ophtalmiques

Related Child Applications (2)

Application Number Title Priority Date Filing Date
EP12152476.3A Division-Into EP2455085B1 (fr) 2005-09-30 2006-09-29 Utilisation topique par application dans l'oeil de l'ivermectine, pour le traitement des pathologies ophtalmiques
EP12152476.3A Division EP2455085B1 (fr) 2005-09-30 2006-09-29 Utilisation topique par application dans l'oeil de l'ivermectine, pour le traitement des pathologies ophtalmiques

Publications (2)

Publication Number Publication Date
EP1933849A2 EP1933849A2 (fr) 2008-06-25
EP1933849B1 true EP1933849B1 (fr) 2016-10-26

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP06842320.1A Active EP1933849B1 (fr) 2005-09-30 2006-09-29 Utilisation d'ivermectine pour le traitement des pathologies ophtalmiques

Country Status (5)

Country Link
EP (1) EP1933849B1 (fr)
JP (1) JP2009510049A (fr)
AU (1) AU2006313447A1 (fr)
CA (1) CA2620814A1 (fr)
WO (1) WO2007054822A2 (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8541022B2 (en) * 2008-06-02 2013-09-24 Galderma S.A. Method of treating burns using avermectin compound
FR2942138A1 (fr) * 2009-02-16 2010-08-20 Galderma Res & Dev Association de composes pour le traitement ou la prevention des affections dermatologiques
US10730901B2 (en) 2018-07-27 2020-08-04 Aperta Biosciences, Llc Spinosyn formulations for treatment of demodex-induced ocular and facial conditions
US20210052490A1 (en) * 2019-08-20 2021-02-25 Vishwanath Padmanabhan Compositions and methods for the treatment of anterior blepharitis and posterior blepharitis

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5614545A (en) * 1988-06-09 1997-03-25 Leonard Bloom Topical composition for treatment of blepharitis
US5318780A (en) * 1991-10-30 1994-06-07 Mediventures Inc. Medical uses of in situ formed gels
TW205503B (en) * 1992-04-24 1993-05-11 Ciba Geigy Ag Apparatus for removing components from solutions
US5952372A (en) * 1998-09-17 1999-09-14 Mcdaniel; William Robert Method for treating rosacea using oral or topical ivermectin
US6133310A (en) * 1999-08-26 2000-10-17 Parks; L. Dean Method of treatment of rosacea
US7897559B2 (en) * 2000-06-29 2011-03-01 Parks L Dean Dermatological composition and kit containing avermectin compound for treating dermatological conditions
EP1385496A4 (fr) * 2001-05-09 2006-03-29 Univ Michigan Compositions pour le traitement de l'acne rosacee
JP4448441B2 (ja) * 2002-06-05 2010-04-07 ユニヴァーシティ オブ フロリダ リサーチ ファウンデーション，インコーポレイテッド 眼科用医薬のデリバリーシステム
EP1600158A1 (fr) * 2004-05-26 2005-11-30 Galderma Research & Development, S.N.C. Compositions pharmaceutiques contenant de l'ondansetron et son utilisation pour le traitement de l'inflammation
FR2867684B1 (fr) * 2004-03-18 2006-05-05 Galderma Sa Gel creme contenant de l'ivermectine

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LOO W J ET AL: "INVERMECTIN CREAM IN ROSACEA: COMPARISON WITH METRONIDAZOLE GEL", BRITISH JOURNAL OF DERMATOLOGY, OXFORD : WILEY-BLACKWELL, UK, vol. 151, 1 July 2004 (2004-07-01), pages 61,ABSTR.NO.P - 92, XP009056313, ISSN: 0007-0963 *
VIDAL: "VIDAL 2003 - Le Dictionnaire", 1 January 2003, VIDAL PUBL., Paris, article "Stromectol 3 mg", pages: 1781 - 1782 *

Also Published As

Publication number Publication date
WO2007054822A3 (fr) 2007-10-04
EP1933849A2 (fr) 2008-06-25
WO2007054822A2 (fr) 2007-05-18
JP2009510049A (ja) 2009-03-12
AU2006313447A1 (en) 2007-05-18
CA2620814A1 (fr) 2007-05-18

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